HYPOTHERMIA INDUCED BY INFUSION OF METHIONINE SULFOXIMINE INTO THE DORSAL RAPHE NUCLEUS OF THE RAT - INVOLVEMENT OF 5-HT(1A) AND GABA(B) RECEPTORS

被引:18
作者
GINEFRIGAYET, M [1 ]
GAYET, J [1 ]
机构
[1] UNIV NANCY 1,FAC SCI,PHYSIOL GEN LAB,BP 239,F-54506 VANDOEUVRE NANCY,FRANCE
关键词
METHIONINE SULFOXIMINE; DORSAL RAPHE NUCLEUS; HYPOTHERMIA; 5-HT RECEPTORS; GABA (GAMMA-AMINOBUTYRIC ACID); GABA RECEPTORS;
D O I
10.1016/0014-2999(93)90136-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
L-Methionine-D,L-sulfoximine (MSO) (25 mug) infused locally into the dorsal raphe nucleus (DRN) induced a progressive decrease in body temperature in conscious restrained rats kept at an ambient temperature of 23-degrees-C. Pretreatment with (+/-)-pindolol (3 mg/kg s.c.) significantly attenuated MSO-induced hypothermia, but pretreatment with ketanserin (0.5 mg/kg i.p.) did not alter either the magnitude or the time course of the decrease in body temperature after intra-DRN infusion of MSO. Local accumulation of gamma-aminobutyric acid (GABA) after infusion of gamma-vinylGABA (10 mug) and (+/-)-nipecotic acid (6 mug) inhibited MSO-induced hypothermia. Blockade of GABA(A) receptors by infusion of (-)-bicuculline (25 ng) had no effect on the decrease in body temperature elicited by MSO, but blockade of GABA(B) receptors by infusion of 2-OH-saclofen (13.3 ng) significantly attenuated MSO-induced hypothermia. In conclusion, local infusion of MSO into the DRN must have slowed down the rate of 5-HT turnover in serotonergic neurons and decreased the release and synthesis of GABA. 5-HT1A somato-dendritic autoreceptors and GABA(B) postsynaptic receptors both appear to be involved in these neurocytochemical processes leading to hypothermia.
引用
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页码:189 / 196
页数:8
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